Top 25 SNPs associated with ALL relapse identified through genome-wide association and multiple rounds of resampling
| SNP information . | Association with ALL relapse in GWAS . | P value for independent prognostic value . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| SNP ID . | Chr . | Position . | Gene . | Risk allele frequency . | Risk allele . | P . | HR (95% CI) . | Validation frequency . | Adjusting for known risk factors . | Within MRD− patients . |
| rs7142143 | 14 | 50473281 | PYGL | 1% | C | 6.72 × 10−9 | 3.61 (2.34-5.57) | 79% | 1.20 × 10−5 | 2.9 × 10−4 |
| rs17079534 | 3 | 39822076 | MYRIP | 0.5% | A | 1.65 × 10−7 | 4.07 (2.4-6.87) | 74% | 2 × 10−4 | 4.74 × 10−5 |
| rs10170236 | 2 | 150165870 | LOC642340 | 25.6% | C | 3.92 × 10−6 | 1.45 (1.24-1.69) | 66% | 5.07 × 10−7 | .0035 |
| rs6683977 | 1 | 66541688 | PDE4B | 44.9% | C | 5.13 × 10−6 | 1.41 (1.22-1.64) | 63% | 5.9 × 10−4 | .081 |
| rs1402612 | 12 | 77517496 | 2.8% | T | 1.85 × 10−5 | 2.45 (1.63-3.69) | 59% | .0059 | 1.1 × 10−4 | |
| rs7578361 | 2 | 150105464 | 27.6% | C | 8.40 × 10−6 | 1.4 (1.21-1.63) | 59% | 1.65 × 10−6 | .0033 | |
| rs17837497 | 7 | 139349062 | TBXAS1 | 1.6% | A | 1.89 × 10−6 | 2.34 (1.65-3.31) | 56% | 6.63 × 10−5 | 7.8 × 10−4 |
| rs1496766 | 7 | 78169401 | MAGI2 | 1.4% | C | 5.45 × 10−6 | 2.84 (1.81-4.44) | 55% | 2.41 × 10−5 | 6.45 × 10−6 |
| rs9958208 | 18 | 38845082 | RIT2 | 9.9% | A | 5.12 × 10−6 | 1.62 (1.32-1.99) | 55% | 1.93 × 10−5 | 4.68 × 10−4 |
| rs9578871 | 13 | 24977627 | ATP8A2 | 33.4% | T | 2.08 × 10−5 | 1.37 (1.18-1.58) | 52% | 7.10 × 10−6 | .0016 |
| rs41322152 | 10 | 71710811 | NPFFR1 | 1.2% | C | 8.33 × 10−6 | 2.52 (1.68-3.79) | 52% | 2.02 × 10−6 | .0027 |
| rs7320729 | 13 | 24962148 | ATP8A2 | 47.2% | T | 1.35 × 10−5 | 1.39 (1.2-1.61) | 51% | 2.69 × 10−6 | 7.77 × 10−5 |
| rs546784 | 1 | 66535054 | PDE4B | 45.7% | A | 9.22 × 10−6 | 1.4 (1.2-1.62) | 51% | .0019 | .087 |
| rs7099696 | 10 | 102946382 | 1.7% | T | 1.17 × 10−5 | 2.57 (1.68-3.92) | 47% | 1.32 × 10−4 | 9.37 × 10−5 | |
| rs12464261 | 2 | 69227954 | ANTXR1 | 46.5% | A | 2.79 × 10−5 | 1.37 (1.18-1.59) | 47% | 6.86 × 10−6 | 7.1 × 10−4 |
| rs879286 | 14 | 32777047 | NPAS3 | 3.3% | G | 2.34 × 10−5 | 1.95 (1.43-2.66) | 46% | 3.49 × 10−6 | 4.9 × 10−4 |
| rs7320702 | 13 | 24975538 | ATP8A2 | 33.5% | A | 2.22 × 10−5 | 1.37 (1.19-1.59) | 45% | 4.20 × 10−6 | 0.0013 |
| rs992435 | 7 | 96888739 | 2.5% | G | 4.66 × 10−5 | 2.12 (1.48-3.04) | 40% | 3.38 × 10−6 | 4.47 × 10−6 | |
| rs6953777 | 7 | 10927258 | 1.2% | C | 4.91 × 10−5 | 2.62 (1.64-4.16) | 39% | 2.4 × 10−4 | .0049 | |
| rs696518 | 3 | 137602990 | STAG1 | 40.9% | C | 4.71 × 10−5 | 1.36 (1.17-1.58) | 39% | .0016 | .015 |
| rs4297844 | 2 | 150108354 | 25.3% | C | 7.60 × 10−5 | 1.36 (1.17-1.58) | 38% | 1.64 × 10−5 | .028 | |
| rs10153318 | 17 | 13265827 | 24.8% | A | 2.10 × 10−5 | 1.41 (1.21-1.66) | 38% | 6.29 × 10−5 | .00965 | |
| rs6538901 | 12 | 98043535 | ANKS1B | 36.5% | G | 6.56 × 10−5 | 1.38 (1.18-1.62) | 37% | .0049 | .011 |
| rs12018180 | 13 | 25035957 | ATP8A2 | 33.2% | A | 7.38 × 10−5 | 1.34 (1.16-1.55) | 37% | 1.7 × 10−4 | 3.2 × 10−4 |
| rs9624873 | 22 | 24260784 | 4.4% | T | 5.50 × 10−5 | 1.8 (1.35-2.39) | 37% | .0058 | .14 | |
| SNP information . | Association with ALL relapse in GWAS . | P value for independent prognostic value . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| SNP ID . | Chr . | Position . | Gene . | Risk allele frequency . | Risk allele . | P . | HR (95% CI) . | Validation frequency . | Adjusting for known risk factors . | Within MRD− patients . |
| rs7142143 | 14 | 50473281 | PYGL | 1% | C | 6.72 × 10−9 | 3.61 (2.34-5.57) | 79% | 1.20 × 10−5 | 2.9 × 10−4 |
| rs17079534 | 3 | 39822076 | MYRIP | 0.5% | A | 1.65 × 10−7 | 4.07 (2.4-6.87) | 74% | 2 × 10−4 | 4.74 × 10−5 |
| rs10170236 | 2 | 150165870 | LOC642340 | 25.6% | C | 3.92 × 10−6 | 1.45 (1.24-1.69) | 66% | 5.07 × 10−7 | .0035 |
| rs6683977 | 1 | 66541688 | PDE4B | 44.9% | C | 5.13 × 10−6 | 1.41 (1.22-1.64) | 63% | 5.9 × 10−4 | .081 |
| rs1402612 | 12 | 77517496 | 2.8% | T | 1.85 × 10−5 | 2.45 (1.63-3.69) | 59% | .0059 | 1.1 × 10−4 | |
| rs7578361 | 2 | 150105464 | 27.6% | C | 8.40 × 10−6 | 1.4 (1.21-1.63) | 59% | 1.65 × 10−6 | .0033 | |
| rs17837497 | 7 | 139349062 | TBXAS1 | 1.6% | A | 1.89 × 10−6 | 2.34 (1.65-3.31) | 56% | 6.63 × 10−5 | 7.8 × 10−4 |
| rs1496766 | 7 | 78169401 | MAGI2 | 1.4% | C | 5.45 × 10−6 | 2.84 (1.81-4.44) | 55% | 2.41 × 10−5 | 6.45 × 10−6 |
| rs9958208 | 18 | 38845082 | RIT2 | 9.9% | A | 5.12 × 10−6 | 1.62 (1.32-1.99) | 55% | 1.93 × 10−5 | 4.68 × 10−4 |
| rs9578871 | 13 | 24977627 | ATP8A2 | 33.4% | T | 2.08 × 10−5 | 1.37 (1.18-1.58) | 52% | 7.10 × 10−6 | .0016 |
| rs41322152 | 10 | 71710811 | NPFFR1 | 1.2% | C | 8.33 × 10−6 | 2.52 (1.68-3.79) | 52% | 2.02 × 10−6 | .0027 |
| rs7320729 | 13 | 24962148 | ATP8A2 | 47.2% | T | 1.35 × 10−5 | 1.39 (1.2-1.61) | 51% | 2.69 × 10−6 | 7.77 × 10−5 |
| rs546784 | 1 | 66535054 | PDE4B | 45.7% | A | 9.22 × 10−6 | 1.4 (1.2-1.62) | 51% | .0019 | .087 |
| rs7099696 | 10 | 102946382 | 1.7% | T | 1.17 × 10−5 | 2.57 (1.68-3.92) | 47% | 1.32 × 10−4 | 9.37 × 10−5 | |
| rs12464261 | 2 | 69227954 | ANTXR1 | 46.5% | A | 2.79 × 10−5 | 1.37 (1.18-1.59) | 47% | 6.86 × 10−6 | 7.1 × 10−4 |
| rs879286 | 14 | 32777047 | NPAS3 | 3.3% | G | 2.34 × 10−5 | 1.95 (1.43-2.66) | 46% | 3.49 × 10−6 | 4.9 × 10−4 |
| rs7320702 | 13 | 24975538 | ATP8A2 | 33.5% | A | 2.22 × 10−5 | 1.37 (1.19-1.59) | 45% | 4.20 × 10−6 | 0.0013 |
| rs992435 | 7 | 96888739 | 2.5% | G | 4.66 × 10−5 | 2.12 (1.48-3.04) | 40% | 3.38 × 10−6 | 4.47 × 10−6 | |
| rs6953777 | 7 | 10927258 | 1.2% | C | 4.91 × 10−5 | 2.62 (1.64-4.16) | 39% | 2.4 × 10−4 | .0049 | |
| rs696518 | 3 | 137602990 | STAG1 | 40.9% | C | 4.71 × 10−5 | 1.36 (1.17-1.58) | 39% | .0016 | .015 |
| rs4297844 | 2 | 150108354 | 25.3% | C | 7.60 × 10−5 | 1.36 (1.17-1.58) | 38% | 1.64 × 10−5 | .028 | |
| rs10153318 | 17 | 13265827 | 24.8% | A | 2.10 × 10−5 | 1.41 (1.21-1.66) | 38% | 6.29 × 10−5 | .00965 | |
| rs6538901 | 12 | 98043535 | ANKS1B | 36.5% | G | 6.56 × 10−5 | 1.38 (1.18-1.62) | 37% | .0049 | .011 |
| rs12018180 | 13 | 25035957 | ATP8A2 | 33.2% | A | 7.38 × 10−5 | 1.34 (1.16-1.55) | 37% | 1.7 × 10−4 | 3.2 × 10−4 |
| rs9624873 | 22 | 24260784 | 4.4% | T | 5.50 × 10−5 | 1.8 (1.35-2.39) | 37% | .0058 | .14 | |
Chromosomal location is based on hg19. Validation frequency represents the number of times a SNP was successfully replicated out of 100 rounds of resampling (see “GWAS for germline SNP genotypes related to risk of relapse”). P values indicate the statistical significance of the associations between SNP genotypes and ALL relapse as determined by Fine and Gray hazard ratio regression model. Hazard ratio (HR) represents the increase in relapse risk for each copy of the risk allele compared with patients who do not carry the risk allele. Independent prognostic value is examined by multivariate analyses adjusting for known relapse risk factors (ie, ancestry, molecular subtypes/lineage, age, leukocyte count at diagnosis, ploidy, and MRD) and by association within patients with negative for MRD at the end of remission induction therapy.
chr indicates chromosome; and CI, confidence interval.